Org. Synth. 1951, 31, 56
DOI: 10.15227/orgsyn.031.0056
ETHYL α-ACETYL-β-(2,3-DIMETHOXYPHENYL)-PROPIONATE
[Hydrocinnamic acid, α-acetyl-2,3-dimethoxy-, ethyl ester]
Submitted by E. C. Horning, J. Koo, M. S. Fish, and G. N. Walker
1.
Checked by T. L. Cairns and Charles W. Todd.
1. Procedure
A.
Ethyl α-acetyl-β-(2,3-dimethoxyphenyl)acrylate. In a
1-l. round-bottomed flask fitted with a
water-benzene separator2 and a
reflux condenser are placed
183 g. (1.1 moles) of 2,3-dimethoxybenzaldehyde (Note 1) and
130 g. (1.0 mole) of ethyl acetoacetate. The water-benzene separator is filled with
benzene, an additional
70 ml. of benzene is added to the mixture, and the
2,3-dimethoxybenzaldehyde is brought into solution by warming.
Piperidine (4 ml.) and
glacial acetic acid (12 ml.) are added, and the mixture is heated under reflux for 2–3 hours
(Note 2). The mixture is cooled, poured into a
separatory funnel with
800 ml. of ether, and washed successively with
200-ml. portions of 5% hydrochloric acid,
5% sodium bicarbonate solution, and
5% acetic acid, and twice with water. The extract is dried over anhydrous
magnesium sulfate (about 250 g.). After filtration, the
ether and
benzene are distilled under atmospheric pressure, and the residue is distilled under reduced pressure. The yield of viscous, yellow oil collected at
186–190°/2 mm. (Note 3) is
180–199 g. (
64–72%),
nD25 1.5507–1.5508.
B. Ethyl α-acetyl-β-(2,3-dimethoxyphenyl)propionate. The product obtained in Part A is divided into two approximately equal portions, and to each are added 125 ml. of ethyl acetate and 5 g. of 5% palladium-on-carbon catalyst (Note 4). Each solution is shaken with hydrogen at pressures between 20 and 40 lb. in a low-pressure apparatus. About 45 minutes is usually needed for complete reduction. The two solutions are then combined, and the catalyst is removed by filtration and washed with 20 ml. of ethyl acetate. The ethyl acetate is distilled at atmospheric pressure, and distillation of the residue under reduced pressure yields 158–176 g. (56–63% over-all) of a colorless product collected at 175–177°/3 mm., nD25 1.5042–1.5044 (Note 3) and (Note 5).
2. Notes
1.
A
practical grade of 2,3-dimethoxybenzaldehyde, although discolored, is satisfactory. It is best handled and weighed as a liquid. This is done by warming the
container on a
steam bath for several minutes.
2.
The time of reflux is determined by the rate at which water separates from the reaction mixture. In general, the theoretical amount of water (18 ml.) is collected in the water separator after about 1 hour, but additional refluxing usually results in the separation of another 4–5 ml. Anhydrous materials are not necessary for the reaction.
3.
Using a
6-in. Vigreux column with a wide side arm, the checkers observed a boiling point of
166–168°/3 mm. for
ethyl α-acetyl-β-(2,3-dimethoxyphenyl)propionate and
176–179°/2 mm. for the
acrylate.
4.
These quantities are convenient for hydrogenation in a Parr low-pressure apparatus; if a larger apparatus is available, it is unnecessary to divide the material. The
palladium-on-carbon catalyst is prepared by Hartung's method,
3 using sufficient
Norit to give a
5% catalyst. A few chips of Dry Ice should be placed in the bottle before the catalyst is added to provide an inert atmosphere. The checkers used a
catalyst obtained from Baker and Company, Inc., 113 Astor Street, Newark, New Jersey.5.
The same procedure may be used with other aromatic aldehydes. The acrylate ester prepared from
veratraldehyde is a crystalline compound melting at
82.5–84.5°. It may be purified by distillation under reduced pressure, b.p.
190–196°/0.8 mm. The yield is
53–63%. The hydrogenated product is obtained as a colorless oil, b.p.
180–183°/1.0 mm., in
38–44% over-all yield.
3. Discussion
Substituted
α-benzylacetoacetic esters have usually been prepared by the general method of Leuchs,
4 in which
ethyl acetoacetate is alkylated in
ethanol solution with
benzyl chloride and
sodium ethoxide. The present method is based upon Cope's
5 procedure for the condensation of carbonyl compounds with
ethyl acetoacetate, followed by catalytic reduction of the condensation product.
This preparation is referenced from:
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
palladium-on-carbon
α-benzylacetoacetic esters
ethanol (64-17-5)
hydrochloric acid (7647-01-0)
acetic acid (64-19-7)
Benzene (71-43-2)
ethyl acetate (141-78-6)
ether (60-29-7)
hydrogen (1333-74-0)
sodium bicarbonate (144-55-8)
Norit (7782-42-5)
piperidine (110-89-4)
sodium ethoxide (141-52-6)
benzyl chloride (100-44-7)
Ethyl acetoacetate (141-97-9)
magnesium sulfate (7487-88-9)
Veratraldehyde (120-14-9)
acrylate
2,3-dimethoxybenzaldehyde (86-51-1)
ETHYL α-ACETYL-β-(2,3-DIMETHOXYPHENYL)-PROPIONATE,
Hydrocinnamic acid, α-acetyl-2,3-dimethoxy-, ethyl ester,
Ethyl α-acetyl-β-(2,3-dimethoxyphenyl)propionate (53608-80-3)
Ethyl α-acetyl-β-(2,3-dimethoxyphenyl)acrylate (19411-81-5)
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